The hypothesis that DNA damage, as distinct from mutation, is the primary cause of aging has not been critically tested. The release of free bases from DNA occurs naturally at a high rate and leads to the formation of apurinic and apyrimidinic lesions. It is important to determine whether an organism's ability to repair these lesions is limited so that they accumulate with time and cause aging. The paramecium is among the simplest eukaryotic organisms in which aging has been shown to occur. Aging in this organism is characterized by a decline in replicative capacity which occurs during asexual reproduction. Rejuvenation or an increase in replicative capacity occurs following sexual reproduction. This investigation is designed to demonstrate (1) that as aging occurs in Paramecium tetraurelia during asexual reproduction apurinic and apyrimidinic lesions and strand breaks or gaps accumulate; and (2) that when paramecium goes through a sexual cycle of reproduction these lesions are repaired. Accumulation of lesions in DNA during the course of normal aging in humans needs critical investigation. Findings from this proposed investigation should increase our insight into which lesions might accumulate, and give rise to aging, in humans. The experiments should also test the idea that sexual reproduction promotes removal of DNA lesions from the germ line, thus preventing "aging" of the DNA passed on to progeny.